Hydrazine hydrate (1:1) → 5-Fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one

HRID 1617265Notes

Reaction equation

HRID 1617265 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:26](OC)=O)[C:5]2[C:6](=O)[CH:7]([C:19]3[N:23]([CH3:24])[N:22]=[CH:21][N:20]=3)[CH:8]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=3)[NH:9][C:10]=2[CH:11]=1.[OH2:30].[NH2:31][NH2:32]>CO>[F:1][C:2]1[CH:11]=[C:10]2[NH:9][CH:8]([C:12]3[CH:13]=[CH:14][C:15]([F:18])=[CH:16][CH:17]=3)[CH:7]([C:19]3[N:23]([CH3:24])[N:22]=[CH:21][N:20]=3)[C:6]3=[N:31][NH:32][C:26](=[O:30])[C:4]([CH:3]=1)=[C:5]23

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 547529555-Quinolinecarboxylic acid, 7-fluoro-2-(4-fluorophenyl)-1,2,3,4-tetrahydro-3-(1-methyl-1H-1,2,4-triazol-5-yl)-4-oxo-, methyl ester2×

Product 1

HCID 1357436815-Fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-oneYield 78.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Methyl 7-fluoro-2-(4-fluorophenyl)-3-(1-methyl-1H-1,2,4-triazol-5-yl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylate (5) (150 g, 0.38 mol, 1.0 eq.) and methanol (1.7 L) were charged into a 3 L 3-neck flask equipped with a mechanical stirrer, thermometer, and nitrogen inlet/outlet. The resulted suspension was stirred at room temperature for 15 minutes. Hydrazine hydrate (85% of purity, 78.1 g, 1.33 mol, 3.5 eq.) was charged dropwise into the above reaction mixture within 30 minutes at ambient temperature. The reaction mixture was stirred at room temperature overnight. The reaction was monitored by HPLC, showing about 2% of compound (5) left. The obtained slurry was filtered. The wet cake was suspended in methanol (2 L) and stirred at room temperature for 3 hours. The above slurry was filtered, and the wet cake was washed with methanol (0.5 L). The wet cake was then dried in vacuum at 45-55° C. for 12 hours. This afforded the title compound as a pale yellow solid (112 g, yield: 78.1%, purity: 95.98% by HPLC). LC-MS (ESI) m/z: 381 (M+1)+. 1H-NMR (400 MHz, DMSO-d6) δ (ppm): 3.66 (s, 3H), 4.97-5.04 (m, 2H), 6.91-6.94 (dd, J1=2.4, J2=11.2 Hz, 1H), 7.06-7.09 (dd, J1=2.4, J2=8.8 Hz, 1H), 7.14-7.18 (m, 3H), 7.47-7.51 (m, 2H), 7.72 (s, 1H), 7.80 (s, 1H), 12.35 (s, 1H).

Workup

  1. customequipped with a mechanical stirrer
  2. stirringThe reaction mixture was stirred at room temperature overnight
  3. waitleft
  4. filtrationThe obtained slurry was filtered
  5. stirringstirred at room temperature for 3 hours
  6. filtrationThe above slurry was filtered
  7. washthe wet cake was washed with methanol (0.5 L)
  8. customThe wet cake was then dried in vacuum at 45-55° C. for 12 hours

Sources & evidence

ORD record
ord-4cc10d3830e846938feb9d0882945a7a
Source dataset
uspto-grants-2014_07
Patent number
US08765945B2

Reaction notes

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